Effect of PCSK9-Antibody (Alirocumab) on Dyslipidemia Secondary to Nephrotic Syndrome

NCT03004001 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: VA16-029
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

The study purpose is to determine the hypolipidemic effect of Alirocumab co-administered with atorvastatin on levels of triglyceride-rich lipoproteins and LDL compared to monotherapy with atorvastatin in patients with dyslipidemia secondary to nephrotic syndrome.

Conditions

Nephrotic Syndrome

Keywords

Severe proteinuria; Dyslipidemia

Outcome Measures

Primary Outcomes (1)

• Levels of plasma lipoproteins

  ion mobility lipoprotein analysis

  up to 10 months

Secondary Outcomes (3)

• Levels of PCSK9

  up to 10 months

• Triglyceride-rich lipoproteins (Remnants)

  up to 10 months

• Lipidomics

  up to 10 months

Study Arms (2)

Alirocumab and atorvastatin

EXPERIMENTAL

Alirocumab 150 mg bi-weekly and atorvastatin 20 mg/d

Drug: Alirocumab; Drug: Atorvastatin

Alirocumab placebo and atorvastatin

PLACEBO COMPARATOR

Alirocumab placebo biweekly and atorvastatin 20 mg/d

Drug: Alirocumab placebo; Drug: Atorvastatin

Interventions

Alirocumab DRUG

150 mg biweekly

Also known as: Praluent

Alirocumab and atorvastatin

Alirocumab placebo DRUG

placebo

Also known as: Praluent placebo

Alirocumab placebo and atorvastatin

Atorvastatin DRUG

20 mg/day

Also known as: Lipitor

Alirocumab and atorvastatin; Alirocumab placebo and atorvastatin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Nephrotic Syndrome (NS) (FSGS, IMN or NS and type 2 DM)
• atorvastatin
• LDL C \>= 70 mg/dl or non-HDL C \>= 100 mg/dl
• Plasma trigycerides \< 800 mg/dl.
• Highly effective methods of contraception for pre-menopausal women
• Post-menopausal women must be amenorrheic for at least 12 months.

You may not qualify if:

• homozygous FH
• Fibrates within 6 weeks of screening visit
• Uncontrolled hypothyroidism
• Known history of hemorrhagic stroke
• Known history of loss of function of PCSK9
• use of systemic corticosteroids unless used as replacement therapy for pituitary/adrenal disease with a stable regimen for at least 6 weeks of randomization
• Previous treatment with at least a single dose of alirocumab or any other anti-PCSK9 monoclonal antibody
• Other conditions or situations per protocol
• Laboratory findings or contraindications to background therapies
• Warnings/precautions of use (when appropriate) as displayed in the respective national product labeling
• Any currently known contra-indication to study drug, pregnancy or breastfeeding of infants.

Sponsors & Collaborators

• Gloria Vega: lead
• Regeneron Pharmaceuticals: collaborator
• Aventis Pharmaceuticals: collaborator

Study Sites (1)

DallasVAMC

Dallas, Texas, 75216, United States

Location

Related Publications (4)

• Vega GL, Grundy SM. Lovastatin therapy in nephrotic hyperlipidemia: effects on lipoprotein metabolism. Kidney Int. 1988 Jun;33(6):1160-8. doi: 10.1038/ki.1988.125.

  PMID: 3165483 BACKGROUND

• Toto RD, Grundy SM, Vega GL. Pravastatin treatment of very low density, intermediate density and low density lipoproteins in hypercholesterolemia and combined hyperlipidemia secondary to the nephrotic syndrome. Am J Nephrol. 2000 Jan-Feb;20(1):12-7. doi: 10.1159/000013549.

  PMID: 10644862 BACKGROUND

• Vega GL, Toto RD, Grundy SM. Metabolism of low density lipoproteins in nephrotic dyslipidemia: comparison of hypercholesterolemia alone and combined hyperlipidemia. Kidney Int. 1995 Feb;47(2):579-86. doi: 10.1038/ki.1995.73.

  PMID: 7723244 BACKGROUND

• Jin K, Park BS, Kim YW, Vaziri ND. Plasma PCSK9 in nephrotic syndrome and in peritoneal dialysis: a cross-sectional study. Am J Kidney Dis. 2014 Apr;63(4):584-9. doi: 10.1053/j.ajkd.2013.10.042. Epub 2013 Dec 4.

  PMID: 24315769 BACKGROUND

MeSH Terms

Conditions

Nephrotic Syndrome; Proteinuria; Dyslipidemias

Interventions

alirocumab; Atorvastatin

Condition Hierarchy (Ancestors)

Nephrosis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urination Disorders; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Study Officials

• Gloria L Vega, PhD

  Dallas VAMC

  PRINCIPAL INVESTIGATOR

• Yin Oo, MD

  Dallas VA Medical Center

  STUDY DIRECTOR

• Michael Concepcion, MD

  Dallas VA Medical Center

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: FED
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator at Dallas VA Medical Center

Study Record Dates

• First Submitted: December 16, 2016
• First Posted: December 28, 2016
• Study Start: January 1, 2017
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: August 19, 2022

Record last verified: 2022-08

Locations

US (1)